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Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.
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Capsaicina , Dor , Canais de Cátion TRPV , Animais , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Capsaicina/farmacologia , Masculino , Feminino , Camundongos , Dor/metabolismo , Dor/genética , Hormônios Esteroides Gonadais/metabolismo , Ciclo Estral/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/efeitos dos fármacos , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Caracteres Sexuais , RNA Mensageiro/metabolismo , RNA Mensageiro/genéticaRESUMO
Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1 , KISS1R , AR and INSR , by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R , INSR and AR showed higher expression in the G3 group ( p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.
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SUMMARY OBJECTIVE: The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. METHODS: This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. CONCLUSION: Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.
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Abstract Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1-nonovariectomized control; G2-ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3-ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4-ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5-ovariectomized animal that received estrogen and genistein; and G6-ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1, KISS1R, AR and INSR, by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R, INSR and AR showed higher expression in the G3 group (p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.
Resumo Objetivo Avaliar os efeitos do estrogênio, raloxifeno e genisteína na expressão de KISS1 (kisspeptina), KISS1R (receptor da kisspeptina), AR (receptor de androgênio) e INSR (receptor de insulina) nos ossos de ratas ovariectomizadas. Métodos Quarenta e oito ratas adultas foram divididas aleatoriamente em 6 grupos, contendo 8 animais cada: G1-controle não ovariectomizado); G2-ovariectomizado e tratado com estrogênios conjugados equinos (50 µg/Kg/dia); G3-ovariectomizado e tratado com raloxifeno (0,75 mg/kg/dia); G4-ovariectomizado que recebeu extrato de soja com genisteína (300 mg/kg/dia); G5-ovariectomizado que recebeu estrogênio e genisteína; e G6-ovariectomizado que recebeu estrogênio e raloxifeno. Após 3 meses da cirurgia, os animais castrados receberam os fármacos diariamente por via oral, durante 120 dias. Todos os animais foram sacrificados após esse período, por aprofundamento da anestesia. A tíbia esquerda foi removida para extração de RNA total e análise da expressão gênica de KISS1, KISS1R, AR e INSR, por reação de cadeia de polimerase quantitativa em tempo real (quantitative real-time polymerase chain reaction, qRT-PCR, em inglês). Resultados KISS1 não foi detectado em nenhum dos grupos tratados. KISS1R, INSR e AR mostraram maior expressão no grupo G3 (p < 0,001), enquanto menores níveis de transcritos para esses genes foram observados em G4 e G5. Os animais de G2 apresentaram hipoexpressão dos genes avaliados. Conclusão Os resultados indicam que o raloxifeno, isolado ou combinado com estrogênio, foi capaz de induzir a expressão de genes associados à recuperação da homeostase do tecido ósseo em ratas ovariectomizadas.
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Animais , Ratos , Osteoporose , Genisteína , Cloridrato de Raloxifeno/uso terapêutico , Estrogênios , KisspeptinasRESUMO
Urinary incontinence due to urethral sphincter mechanism incompetence (USMI) affects up to 20% of bitches that undergo spaying surgery. Amitriptyline is a tricyclic antidepressant whose urinary retention is a reported side effect. This study aimed to assess the efficacy and safety of amitriptyline when compared to estriol orally. Fifteen bitches with a clinical diagnosis of post-spaying UI were evaluated during 60 days in a non-blinded randomized clinical trial. All patients were enrolled after clinical evaluation consisting of anamnesis, physical examination, and complementary exams (complete blood count, biochemical parameters, urinalysis, and abdominal ultrasound). The amitriptyline (AMT) group consisted of 8 bitches, which received the initial dose of 1 mg/kg every 12 h, whereas the estriol (EST) group consisted of 7 bitches which were initially treated with 1 mg/animal every 24 h. Patients underwent clinical evaluation at 7 days, and then at 21 and 60 days of treatment to assess safety and efficacy, as well as adjustments of dose when necessary. A urinary incontinence scale was used to assess the level of incontinence and therapeutic response to treatment. During the period of the study, estriol was fully effective in 71% of cases and amitriptyline in 62%. Both drugs proved safe in the medical treatment of USMI, with adverse effects such as somnolence (AMT, n = 5/8) and male attraction (EST, n = 1/7). The results support the amitriptyline recommendation as a substitute for estriol in USMI treatment.
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Doenças do Cão , Enurese , Incontinência Urinária , Feminino , Masculino , Animais , Cães , Amitriptilina/uso terapêutico , Ovariectomia/veterinária , Doenças do Cão/diagnóstico , Incontinência Urinária/tratamento farmacológico , Incontinência Urinária/veterinária , Incontinência Urinária/diagnóstico , Enurese/etiologia , Enurese/veterináriaRESUMO
Los síntomas vasomotores (SVM) asociados a la menopausia suelen disminuir la calidad de vida de las mujeres, al generar un elocuente malestar. La terapia hormonal de la menopausia (THM) es el estándar en el tratamiento de los síntomas de la menopausia, siendo el único tratamiento que ha demostrado ser eficaz para los SVM. Objetivo: describir la eficacia y seguridad de la terapia hormonal de la menopausia vía transdérmica (THM TD) para aliviar los síntomas de la menopausia. Métodos: se hizo una revisión sistemática de la literatura en diferentes bases de datos electrónicas (CINAHL Plus, EMBASE, Scopus, Lilacs, Medline, Pubmed, entre otras), a través de términos de búsqueda estandarizados. Los desenlaces evaluados incluyeron los estudios donde se publicó cualquier tratamiento o intervención con la THM TD en mujeres tratadas por síntomas de la menopausia, porcentajes de alivio de los síntomas climatéricos y proporción de eventos adversos asociados. Resultados: se incluyeron 45 publicaciones, y convienen en aconsejar el tratamiento con la THM TD, en vista de un alivio de los síntomas climatéricos cerca del 90%, asimismo de ser más segura y potencialmente más eficaz que la terapia oral; con resultados normales en la evaluación mamográfica, y sin eventos adversos relacionados después de 5 años de seguimiento. Conclusiones: la terapia hormonal en la menopausia vía transdérmica es segura y eficaz para aliviar los síntomas de la menopausia. Al evitarse el metabolismo hepático, alcanza mejores beneficios clínicos, a la vez que minimiza la exposición de eventos adversos. Las publicaciones revisadas demuestran que la vía transdérmica es la mejor forma de tratar los síntomas de la menopausia.
Vasomotor symptoms (VMS) associated with menopause usually reduce the quality of life of women, generating eloquent discomfort. Menopausal hormone therapy (MHT) is the standard in the treatment of menopausal symptoms, being the only treatment that has been shown to be effective for VMS. Objective: to describe the efficacy and safety of transdermal menopausal hormone therapy (THM TD) to relieve menopausal symptoms. Methods: a systematic review of the literature was carried out in different electronic databases (CINAHL Plus, EMBASE, Scopus, Lilacs, Medline, Pubmed, among others), through standardized search terms. The outcomes evaluated included studies where any treatment or intervention with TD MHT was published in women treated for menopausal symptoms, percentages of relief of climacteric symptoms and proportion of associated adverse events. Results: 45 publications were included, and they agree in advising treatment with MHT TD, in view of a relief of climacteric symptoms close to 90%, as well as being safer and potentially more effective than oral therapy; with normal results in mammographic evaluation, and without related adverse events after 5 years of follow-up. Conclusions: transdermal hormonal therapy in menopause is safe and effective in relieving menopause symptoms. By avoiding hepatic metabolism, it achieves better clinical benefits, while minimizing the exposure to adverse events. The reviewed publications demonstrate that the transdermal route is the best way to treat menopause symptoms.
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Acetylcholine (ACh) is a neurotransmitter that regulates multiple functions in the nervous system, and emerging evidence indicates that it could play a role in cancer progression. However, this function is controversial. Previously, we showed that organophosphorus pesticides decreased the levels of the enzyme acetylcholinesterase in vivo, increasing ACh serum levels and the formation of tumors in the mammary glands of rats. Furthermore, we showed that ACh exposure in breast cancer cell lines induced overexpression of estrogen receptor alpha (ERα), a key protein described as the master regulator in breast cancer. Therefore, here, we hypothesize that ACh alters the ERα activity through a ligand-independent mechanism. The results here reveal that the physiological concentration of ACh leads to the release of Ca+2 and the activity of MAPK/ERK and PI3K/Akt pathways. These changes are associated with an induction of p-ERα and its recruitment to the nucleus. However, ACh fails to induce overexpression of estrogen-responsive genes, suggesting a different activation mechanism than that of 17ß-estradiol. Finally, ACh promotes the viability of breast cancer cell lines in an ERα-dependent manner and induces the overexpression of some EMT markers. In summary, our results show that ACh promotes breast cancer cell proliferation and ERα activity, possibly in a ligand-independent manner, suggesting its putative role in breast cancer progression.
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Pharmaceuticals and endocrine disrupting compounds are organic micropollutants that can cause adverse effects at low concentrations. Their occurrence in surface waters has been reported in several countries, including Brazil, at concentrations on the order of ngL-1, while the concentrations at which toxic effects are observed are often in the range of mg.L-1 to µg.L -1, however few studies have been undertaken to characterize risks they represent in Brazilian surface waters. Thus, the objective of this study was to evaluate the ecological risk to Brazilian surface waters caused by the presence of pharmaceuticals and natural and environmental estrogens. Twenty-nine pharmaceuticals, hormones and environmental estrogens were included in the risk assessment while twelve were discarded due to insufficient data availability. The endocrine disrupting compounds were the most frequently detected (39.8% of the reported concentrations), followed by non-steroidal anti-inflammatory drugs (16.3%), antibiotics (6.6%), antiseptics (5.1%), analgesics (5.1%), antihypertensives (4.6%), and to a lesser extent, lipid controllers, anticonvulsants, antidepressants, antihistamines, antivirals and corticosteroids. Bisphenol-A was the most frequently detected compound, followed by diclofenac, 17-ß-estradiol, 17-α-ethynilestradiol, naproxen, triclosan and 4-n-nonylphenol. Acute ecological risk was predicted in two thirds and chronic risk in one third of the water bodies surveyed. The presence of diclofenac or triclosan was determinant for acute risk while estrogenic hormones proved to be decisive for chronic risk. In addition to natural and synthetic endocrine disruptors, the pharmacological groups estimated to have the highest average associated risks were non-steroidal anti-inflammatory drugs, followed by anticonvulsants. No discharge limits exist for most of the compounds found to contribute to ecological risks, indicating the need for regulatory action by the proper Brazilian authorities.
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Disruptores Endócrinos , Triclosan , Poluentes Químicos da Água , Disruptores Endócrinos/análise , Brasil , Diclofenaco , Anticonvulsivantes , Poluentes Químicos da Água/análise , Estrogênios/análise , Estradiol/análise , Anti-Inflamatórios não Esteroides , Medição de Risco , Preparações Farmacêuticas , Monitoramento AmbientalRESUMO
Sexuality in people with mental disorders is a topic usually tinged with prejudice and stigma. Women with severe mental disorders are more exposed to suffer sexually transmitted diseases, becoming victims of gender violence and being involved with unintended pregnancies. In adults and adolescents, sexual intercourse under the influence of alcohol or other drugs, or during worsening or exacerbation of baseline symptoms or condition, are often unplanned, unprotected, with casual partners from high risk groups, without contraceptive methods and with less capacity to agree or deny safe sexual practices. Sexual and reproductive rights as well as gender perspective need to be considered an integral part of women with mental disorders health being and treatment. For this reason, discussing with patients about their desire or not to have children, their sexual life and provide them the most adequate options of contraceptive methods taking into consideration their needs so that and informed decision should be part of the psychiatric consultation. Hormonal contraceptives are widely used globally, being one of the most prescribed groups of drugs. It is estimated that more than 100 million women take oral contraceptives to prevent pregnancy, to treat menstrual pain and/or menstrual heavy bleeding or to control acne. Oral contraceptives result from the combination of estrogen and progestin derivatives, or progestins alone. This review will focus on the description of each hormonal contraceptive methods and hormone replacement therapy and the special features of their concomitant use with psychotropic drugs during treatment of women with psychiatric disorders.
La sexualidad de las personas con trastornos mentales es una temática habitualmente teñida de prejuicios y estigma. Las mujeres con trastornos mentales severos presentan mayor vulnerabilidad a padecer enfermedades de transmisión sexual, ser víctimas de violencia de género y tener embarazos no intencionales. En adultas y adolescentes, las relaciones sexuales bajo la influencia del alcohol o de otras drogas, o en momentos de descompensación de su cuadro de base son a menudo no planificadas, con parejas de riesgo, sin métodos anticonceptivos y con menor capacidad para negociar prácticas sexuales seguras. Desde una perspectiva de género y de derechos humanos, en la atención de mujeres con trastornos mentales, es necesario incluir los derechos sexuales y reproductivos como parte del tratamiento. Por tal motivo, hablar con nuestras pacientes sobre sus deseos de tener hijos, o no, sobre su vida sexual y la provisión de un método anticonceptivo acorde a su elección y necesidades, forma parte de la consulta psiquiátrica. Los anticonceptivos hormonales están ampliamente utilizados a nivel global, constituyendo uno de los grupos de fármacos más prescriptos. Se estima que más de 100 millones de mujeres los consumen para evitar el embarazo, como tratamiento de los sangrados abundantes, las menstruaciones dolorosas o el acné. Resultan de la combinación de derivados estrogénicos y progestágenos, o progestágenos solos. En esta revisión se focalizará en la descripción de los diversos métodos anticonceptivos hormonales, en la terapia hormonal de reemplazo y en las particularidades del uso simultáneo con psicofármacos en mujeres tratadas por trastornos psiquiátricos.
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Anticoncepcionais , Terapia de Reposição Hormonal , Humanos , Feminino , Psicotrópicos , Estudos RetrospectivosRESUMO
Introduction: it seems that, in the phase of greatest fertility, women's intrasexual competition (toward attractive women who live nearby) increases due to access to resources, status, and biologically desirable partners. Objective: to compare the economic decisions (ED) during the ovulatory (OP) and luteal (LP) phases of the menstrual cycle (MC) with exposure to two stimuli: a photograph of a more attractive woman and a photograph of a less attractive woman, through the ultimatum game (UG). Methodology: the research followed a cross-sectional design between subjects to see group diï¬erences by contrasting hypotheses. The sampling was probabilistic, with a sample of 100 heterosexual women, students at a public university with an age range of 18 to 24 years, with regular MC, who did not use hormonal contraceptive methods and did not have any endocrine condition. The inverse counting method with conï¬rmation was applied to identify CM phases; and the UG to evaluate the DE. Results: the phases of the MC had no eï¬ect on the ED; the women behaved similarly in their decisions, regardless of the phase of the cycle they were in or the type of stimulus to which they were exposed. Conclusion: OP and LP do not aï¬ect the ED of women when they are exposed to an attractive stimulus. The discussion is made considering the evolutionary theory of the ovulatory shift hypothesis.
Introducción: parece ser que, en su fase de mayor fertilidad, la competencia intrasexual de la mujer (con mujeres atractivas y que viven cerca) aumenta por el acceso a recursos, estatus y parejas biológicamente deseables. Objetivo: comparar las decisiones económicas (DE) en las fases ovulatoria (FO) y lútea (FL) del ciclo menstrual (CM) con exposición a dos estímulos: fotografía de una mujer de mayor atractivo y fotografía de una mujer de menor atractivo, a través del juego del ultimátum (UG). Metodología: la investigación tuvo un diseño cross-sectional entre sujetos para ver diferencia de grupos mediante contraste de hipótesis. El muestreo fue probabilístico, con una muestra de 100 mujeres heterosexuales, estudiantes de una universidad pública con un rango de edad de 18 a 24 años, con CM regulares, que no usaran métodos anticonceptivos hormonales y no tuvieran ninguna afección endocrina. Resultados: las fases del CM no tuvieron efectos sobre las DE; las mujeres se comportaron de forma similar en sus decisiones, sin importar la fase del ciclo en la que se encontraban o el tipo de estímulo al que fueron expuestas. Conclusión: las FO y FL no afectan las DE de las mujeres cuando son expuestas a un estímulo atractivo. La discusión se hace a la luz de la teoría evolutiva de la hipótesis del cambio ovulatorio.